The objective of this research is to study the mechanism of insulin release (IR) from pancreatic islet cells in hopes that this may provide clues to understanding the defective insulin release response characteristic of diabetic patients. Specifically, we will be studying the role of islet cell membrane electrical potential as a signal in the stimulation-secretion coupling of insulin release. Islet cell electrical activity (EA) is measured with glass microelectrodes in the isolated perifused mouse pancreas. Goals of the study are to characterize: 1) the membrane electrical response to both secretory and subsecretory concentrations of bath glucose, 2) the impact of the adrenergic agents (known to be regulators of IR) on these glucose induced responses and 3) the role of membrane electrical events in the IR process. Results will be interpreted with respect to an hypothesis which states that glucose-induced depolarization of islet cells stimulates EA, which in turn stimulates IR, and that adrenergic effects on IR may be mediated via changes in EA.